P859 Introduction: New onset post-transplant diabetes mellitus (PTDM) has become increasingly recognized complication of kidney transplantation. Albeit, in the majority of studies during the past decade PTDM rate was found to be significantly higher among patients receiving tacrolimus than cyclosporine, there are major center differences in the reported incidence of PTDM as well as controversy as to the extent of diabetogenicity of tacrolimus (Tac) vs. cyclosporine (Csa). Aim: In this study, we aimed to determine the incidence and dynamics of PTDM in a cohort of consecutive renal transplant recipients remaining on Csa or switched to Tac and followed up for 5 years. Methods: We studied records of all consecutive renal graft recipients (n 107), excluding those with pretransplant diabetes mellitus, transplanted in 1998 and followed up throughout 1998-2003 for new onset of PTDM, defined as de-novo hyperglycemia (glucose >120 mg/dL) treated for more than 1 month. The posttransplant immunosuppression consisted of Csa (Neoral) – started at 10 mg/kg and adjusted to blood levels of 300ng/ml (0-3 mos), 200-250 ng/ml (3-6 mos), 150-200 ng/ml (6-12 mos), 100-150 ng/ml (> 12 mos) or Tac- started at 0.15 mg/kg and adjusted to blood levels of 15-20 ng/ml (0-1 mos), 10-15 ng/ml (1-6 mos), 5-10 ng/ml (>6 mos) given in conjunction with prednisone - 500 mg/d of solumedrol, followed by prednisone 100 mg/d >30 mg/d > 20 mg/d > 10 mg/d tapering over 6 months, azathioprine – at 150 mg/d, or replaced by mycophenolate mofetil - 1.0-2.0 gr/d. The patients were divided into 2 groups: those remaining on Csa (n 43) and those started (n 19) or switched to Tac (n 45). Patient demographics, PRA, HLA match, donor organ parameters, incidence of PTDM, graft and patient survival, and renal function in patients on Csa (Neoral) and Tac were compared, when appropriate, by Wilcoxon Two-Sample, Chi-Square, Fisher’s Exact, T test, Gehan-Wilcoxon, Cox-Mantel, Log rank and Kaplan-Meier tests (SAS statistical software). Results: PTDM was detected in 12/107 patients (11.2%). At the time of its appearance, PTDM prevalence in patients under Tac and Csa -5/50 (10%) and 7/57 (12.2%), respectively was not significantly different (Fisher, Chi test NS). Highest prevalence of new PTDM cases was observed in the first post-transplant year – 11/12 cases (91.7%). In contrast to some previous reports, mellow slope of the PTDM increase was observed on predominantly low-dose FK based protocol after the first year, with the calculated annual elevation of 0.25% in the posttransplant years 2-5. Conclusions: Our results show the PTDM cumulative 5 year incidence of 11.2%. No significant difference in PTDM incidence was found between Csa and Tac treatment (12.2% and 10% over 5 years, respectively). Therefore, it appears that in comparison with Csa immunosuppression, our current, tacrolimus-based protocol is not associated with the increased incidence of PTDM.

P757 Aims: Five doses of daclizumab given initially after kidney transplantation have been shown to reduce acute rejection (AR). Most previous studies with daclizumab were performed mainly in cyclosporine treated recipients and only few were done in patients on tacrolimus-based protocol. The aim of this study was to determine the safety and efficacy of two doses of daclizumab combined with tacrolimus (Tac), mycophenolate mofetil (MMF) and corticosteroids (CS) in prevention of acute rejection in primary kidney allograft. Methods: 25 patients were recruited and randomized into induction (n=11) and control (n=14) groups. All patients received initially 0.15mg/kg of Tac tapered to 0.1mg/kg (mean blood levels 10.9 +/− 2.5 ng/dL at first 3 months, 9.5 +/− 2,9 ng/dL at 6 months and 7.9+/− 2.0 ng/dL at one year), MMF at 2gr/bw/day and CS tapered from 100 to 10 mg/bw/day at 6 month. The induction group received two doses of 1mg/kg daclizumab: before engraftment and on postoperative day 14. All patients received CMV prophylaxis with oral gancyclovir. Patient demographics, PRA status and donor organ characteristics were not significantly different between induction and study group. The mean follow up was 16.8 +/− 4,3 months. Fisher Exact and Student T tests were used as appropriate to compare groups. Results: At one year, biopsy proven AR was diagnosed in 5/14 (35%) of control patients not receiving daclizumab and in none of patients with induction (0/11, 0%) (p 0.05). One patient from control group died from cardiac infarction with functioning renal graft. Delayed graft function, defined as absence of spontaneous reduction of creatinine requiring dialysis support, occurred in 6 out of 14 patients (42.8%) from the control group and in 3/11 (27%) patients treated with daclizumab, p NS. Mean creatinine at one year was 1.47+/−0.8 mg/dL in induction and 1.55+/−0.9 mg/dL in control group (NS), the non censored one year patient and graft survival was 100%/100% and 92.8%/ 85.7% (NS) in daclizumab and control group respectively. There were no adverse effects related to daclizumab administration. The infectious complications (UTI and wound infections) occurred in 5/11 and 9/14 (NS) patients from induction and control groups respectively. Conclusions: Our data suggest that the two doses of daclizumab combined with tacrolimus-MMF-CS protocol is effective in preventing acute rejection, reducing incidence of delayed graft function rate and in maintaining satisfactory graft function. The additional advantages of limited dose daclizumab-tacrolimus combination protocol, could be it’s cost effectiveness as well as lesser likelihood of development of neutralizing anti-daclizumab antibodies.

BACKGROUNDRecent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.OBJECTIVESTo study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants.METHODSBetween September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.RESULTSLUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.CONCLUSIONSDespite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Objectives. Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation.Methods. Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters.Results. LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01).Conclusions. Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants. (C) 2003 Elsevier Inc.

Background & aims: Nutrition can interfere with organ function during the different stages of transplantation. Oral fish oil supplementation to kidney transplant recipients has been found to improve renal function. The aim of the present study was to determine the safety and tolerance of intravenous administration of fish-oil emulsion to heart-beating brain-dead donors and, subsequently, to the kidney recipients, and to assess its effects on renal function.Methods: A lipid emulsion enriched with omega-3 fatty acids (MLF 541) was given intravenously to 8 heart-beating, brain-dead organ donors for up to 4 h before organ harvesting and to the kidney recipients for 5 days postoperatively. Hemodynamic, biochemistry and hematological parameters were measured before and at the end of lipid administration in the donors and on posttransplantation days 1, 5, 30 and 180 in the recipients. Findings in the recipients were compared with a concurrent control group.Results: There were no significant changes in hemodynamic or laboratory parameters during the MLF infusion in the donors or the 5 days of MLF administration in the recipients. Blood urea nitrogen and serum creatinine Levels decreased over time in both the study and control recipients (P<0.05 for both), with no significant between-group difference at any of the time points studied.Conclusions: Administration of MLF 541 is safe in organ donors and in kidney recipients. Further studies involving nutrients as pharmacological agents in organ transplantation are warranted. (C) 2003 Elsevier Ltd. All rights reserved.

BK POLYOMA virus (BKV) is a newly described agent causing renal dysfunction and failure among kidney transplant recipients. The virus remains latent following primary exposure at childhood and becomes activated in immunocompromised states. Clinically, the virus rarely causes symptoms such as hemorrhagic cystitis in bone marrow transplant recipients. Although viral shedding is detected in urine specimens of many renal transplant recipients, only a few will develop BKV transplant nephropathy. This disease process is characterized by a rapidly progressive loss of graft function. Introduction of new and more aggressive immunosuppressive protocols may explain the emergence of this new infectious complication. We describe our experience with 7 patients with BKV nephropathy with specific attention to possible risk factors.

BACKGROUND:Cyclosporin A has been associated with severe toxic side effects in patients with familial Mediterranean fever who underwent renal transplantation. Nevertheless, the impact on graft function and survival is not well documented.OBJECTIVE:To compare long-term graft function and survival, between CsA-based vs. CsA free immunosuppressive protocols in FMF recipients of renal allograft.METHODS:Data of FMF recipients were analyzed retrospectively. Graft survival and function and the incidence of acute rejection were correlated to graft source (living donor vs. cadaveric donor), colchicine dose, presence of proteinuria, and immunosuppression protocol (CsA-based triple drug therapy vs. azathioprine-prednisone alone).RESULTS:There were 35 FMF patients with primary renal grafts (13 from living donors and 22 from cadaveric donors). Mean follow-up was 10.6 +/- 6.05 years. Sixteen patients were on CsA-based triple drug therapy and 19 patients on AZA-Pred alone. Mean overall graft survival was 11.2 +/- 0.6 years and 9.4 +/- 1.36 vs. 11.6 +/- 0.4 years for CsA-treated and AZA-Pred groups respectively (P = 0.05). One-year survival was 94% and 96.6% for CsA-treated vs. non-CsA patients (not significant), but 5 and 10 years survival were 76% and 46%, compared to 94.5% and 86% respectively (P = 0.05 at 5 years and 0.001 at 10 years). Mean serum creatinine at time of data collection was 2.3 +/- 1.5 mg/dl in the CsA group vs. 1.6 +/- 0.7 mg/dl in the AZA-Pred group (P = 0.02). There were 14 and 13 reversible rejection episodes in the AZA-Pred and CsA groups respectively (not significant).CONCLUSION:It is suggested that CsA exerts detrimental effects on long-term renal graft function and survival in FMF patients.

1Dept. of Transplantation, Rabin Medical Center, Petach-Tikva, Israel;2Institute of Chemical Pathology, Sheba Medical Center, Ramat-Gan, Israel.

After kidney transplantation, recurrence of primary or secondary glomerulonephritis or de novo nephropathy occurs quite commonly, globally involving up to 20%–25% of patients. Different incidences, timings of recurrence, and rates of aggressiveness have been reported according to the specific disorder observed. A correct diagnosis is mandatory but not all the time easy to be obtained. Specific therapies must be taken into account according to the diagnosed underlying disease.

652 The aim of this study was to compare efficacy and safety of lipid -lowering diet with HMG-Co reductase inhibitor treatment in renal transplant recipients (TxR) with hyperlipidemia (HL). Despite wide agreement on the serious risks and on the need for aggressive treatment of HL, no consensus has yet been reached on the best management of HL in transplant population. This is because some investigators have found that the diet alone is inadequate, while others point out to the side effects of lipid-lowering drugs. We prospectively studied 30 TxR (21 males and 9 females, aged 24-57 yrs.) presenting with HL at 3-6 mos. after renal transplantation. All patients were immunosuppressed with csa-aza-pred and had stable renal function, no proteinuria or liver dysfunction. The patients were prospectively randomized in 3 groups of 10 pts. each: 1.control-C which received routine dietary recommendations, 2.diet-D which received detailed lipid-lowering diet and was under close supervision of the dietitian, and 3.medication-M which received 10 mg/day of Simvastatin (5pts.) or 20 mg/day of Fluvastatin (5 pts.). All patients were followed up for 3 mos., with monthly physical examinations and biochemical and lipid profile studies. Patients diet and caloric intake were recorded using RECALL questionnaires filled by pts. twice a week. The results are shown in table 1.:TableAt the end of follow up and up to the present no adverse effects or changes in hepatic or renal function were observed in group with medications. Conclusions: in this study HMG-Co reductase inhibitors were found effective and significantly superior to diet in lowering total and HDL cholesterol and in restoration of more favorable LDL/HDL ratio. Post-transplant HL was found generally to be more resistant to dietary treatment, which was effective only in reduction of body weight. These findings, together with demonstrated safety of HMG-Co reductase inhibitors, suggest that these agents may be recommended as first line treatment of post-transplant hyperlipidemia.

Some dialyzed patients suffer from lower urinary tract (LUT) anatomic and functional disturbances. Complete LUT assessment should be performed to decide whether they can be included on the waiting list, because such disorders, if not diagnosed and properly treated before transplant, may lead to graft loss.Based on data in the medical records of 4170 dialysis patients, 535 were selected for further investigation: 265 patients after undergoing urethrocystography or urethrocystoscopy, were included on the waiting list for transplantation and 145 patients underwent nephroureterectomy owing to reflux, nephrolithiasis, polycystic renal disease, or hydronephrosis. Five patients with urethral or bladder neck stricture underwent urethral dilation or bladder neck incision. These patients were also ultimately listed for transplantation. Twenty-two patients, with serious LUT disease were qualified for kidney transplantation after extra-anatomic urine outflow. Ninety-eight patients underwent a urodynamic study (URD) to assess LUT disturbances.Of 535 studied patients, 460 (86%), including those who underwent surgical or pharmacologic treatment, were ultimately listed for kidney transplantation. Out of 98 patients who underwent a URD, 45 (46%) were included for kidney transplantation, and 47 for transplantation with atypical urinary outflow. Six patients were excluded from transplantation owing to refusal of investigations or serious contraindications.All potential kidney recipients should undergo proper evaluation of the LUT before being qualified for kidney transplantation. This study allows selection of patients who should undergo surgical and/or pharmacologic treatment before transplantation.

The last decade has witnessed an explosion in the development of new immunosuppressive agents targeted to distinct components of the immune response. This article reviews the basic mechanisms associated with allograft rejection, outlines contemporary immunosuppressive strategies, and discusses the mechanisms of action and roles of contemporary and potential future immunosuppressive agents.

Due to a shortage of suitable kidneys for transplantation there has been an increase in the use of kidneys taken from old and marginal donors, which has led to a high incidence of acute tubular necrosis. Several reports suggest that the administration of calcium channel blockers improves the initial function after renal transplantation. We conducted a randomized, double-blind placebo-controlled trial to study the effect of the calcium channel blocker gallopamil on the incidence and course of acute tubular necrosis following cadaveric renal transplantation. A trend developed showing a decrease in episodes of acute tubular necrosis in gallopamil versus placebo, and became statistically significant when the outcome of kidneys from donors older than 50 years was analyzed separately [gallopamil 6/14 (42%) vs. placebo 10/11 (91%), P < 0.01 corrected chi(2)]. We conclude that pre-transplantation renal graft perfusion and post-transplantation recipient treatment with gallopamil reduces the incidence of post-transplantation acute tubular necrosis, particularly in kidney taken from older donors.